In further approaches to pathogenetic mechanisms operative in rheumatic fever and rheumatic heart disease, it is proposed to separate and characterize a heart valve fibroblast protein antigen which has been found immunologically cross-reactive with group A streptococcal cell membranes. Its relationship to the streptococcal antigens cross- reactive with cardiac myofibers and smooth muscle, previously described, will be determined. Valvular tissue, human and bovine, will be subjected to various extraction techniques, and the antigen, separated by exchange chromatography and sephadex-filtration, will be further defined by physico-chemical and immunochemical methods, employing specific antisera, anti-streptococcal sera, and sera of patients with acute rheumatic fever. The purified antigen will be employed for studies of cellular immunity, e. g., lymphocyte-blast transformation and MIF production in rheumatic individuals. Cellular and humoral immunity to this valvular antigen will be investigated in experimental animals. Its capacity to induce valvular disease will be studied. The biologic properties of C-reactive protein (CRP) will be examined in relation to (a) its capacity to activate the complement system at sites of experimental inflammatory lesions, and (b) the specificity of CRP for choline phosphatides where deposited at sites of tissue necrosis.